Influenza A virus is a virus with high morbidity, high mortality and high contagion. Influenza A virus can use birds or pigs as reservoir hosts in order to continuously spread and exist among different species, produce antigenic shifts through genetic reassortment, and overcome the species barrier to infect humans. Moreover, antigenic drifts caused by quick and unpredictable mutations of the influenza A virus causes people who have been infected with the influenza A virus to be infected again. Because of these two antigenic evolutionary mechanisms, an epidemic or pandemic influenza occurs every few years or decades. Millions of people are infected every year, causing a tremendous burden to health and the economy.
A microRNA (abbreviated miRNA) is a small RNA molecule containing about 22 nucleotides. After transcription, a primary miRNA (pri-miRNA) is cleaved by RNase III enzyme Drosha in the nucleus, and RNase III enzyme Drosha can cleave the double stranded pri-miRNA near the stem-loop and produce a precursor-miRNA (pre-miRNA) having a stem-loop structure and 60-70 nucleotides. Pre-miRNA is exported out of the nucleus by Exportin-5. In the cytoplasm, the pre-miRNA hairpin is cleaved by the RNase III enzyme Dicer, yielding a miRNA:miRNA* duplex about 22 nucleotides in length, and one strand of the miRNA:miRNA* duplex is incorporated into the RNA-induced silencing complex (RISC). The function of the RISC is protein translation inhibition.
In recent years, substantial literature has indicated that miRNA can regulate viral replication. However, whether there exists a species-specific miRNA which can regulate influenza A viral replication remains unknown.